Aberrant methylation of CpG island-containing gene promoters is involved in the inactivation of a number of important mediators of tumor development, including the retinoblastoma gene, the estrogen receptor gene, the E-cadherin gene, and the p16INK4a gene. Previous work in the laboratory has led to the development of a system to induce hypermethylation of CpG islands in human fibroblasts. Through this system, our laboratory has identified a novel gene which is a target for methylation- induced silencing, called TMS-1. Expression of TMS-1 is inactivated in a number of cancer cell lines and may play a role in apoptosis, as suggested by the presence of a structural domain specific to proteins that participate in the caspase cascade. Thus, silencing of this gene may contribute to escape from apoptosis, a powerful selective advantage in establishing carcinogenesis. The primary focus of this proposal is to define the functional role of TMS-1.
The specific aims are to determine whether TMS-1 contributes to apoptosis or growth arrest when introduced into cultured cells, and to identify proteins with which TMS-1 interacts. The characterization of gene related to cancer development that are targets of methylation-associated silencing can provide a basis for future development of demethylation strategies in the treatment of human neoplastic diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA083289-03
Application #
6377522
Study Section
Special Emphasis Panel (ZRG1-SSS-1 (01))
Program Officer
Lohrey, Nancy
Project Start
2001-07-01
Project End
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
3
Fiscal Year
2002
Total Cost
$50,116
Indirect Cost
Name
Emory University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322